P37058 (DHB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Testosterone 17-beta-dehydrogenase 3
EC=1.1.1.64

Alternative name(s):
17-beta-hydroxysteroid dehydrogenase type 3
Short name=17-beta-HSD 3
Testicular 17-beta-hydroxysteroid dehydrogenase

Gene names

Name:	HSD17B3
Synonyms:	EDH17B3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	310 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Favors the reduction of androstenedione to testosterone. Uses NADPH while the two other EDH17B enzymes use NADH.
Catalytic activity	Testosterone + NADP+ = androst-4-ene-3,17-dione + NADPH.
Pathway	Hormone biosynthesis; testosterone biosynthesis.
Tissue specificity	Testis.
Involvement in disease	Male pseudohermaphrodism with gynecomastia (MPH) [MIM:264300]: These individuals have unambiguous female external genitalia at birth, but fail to menstruate at the time of expected puberty and instead virilize as evidenced by growth of the phallus. Breast development may or may not take place. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism Steroid biosynthesis
Coding sequence diversity	Polymorphism
Disease	Disease mutation Pseudohermaphroditism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	androgen biosynthetic process Traceable author statement. Source: Reactome male genitalia development Traceable author statement Ref.1. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome testosterone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	nucleotide binding Inferred from electronic annotation. Source: InterPro testosterone 17-beta-dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 310	310	Testosterone 17-beta-dehydrogenase 3		PRO_0000054573
Regions
	Nucleotide binding	48 – 77	30	NADP By similarity
Sites
	Active site	198	1	Proton acceptor By similarity
	Binding site	185	1	Substrate By similarity
Natural variations
	Natural variant	31	1	V → I. Ref.2 Corresponds to variant rs2066480 [ dbSNP | Ensembl ].		VAR_014870
	Natural variant	56	1	A → T in MPH; Cambridge-2. Affects NADPH cofactor binding. Ref.6		VAR_016067
	Natural variant	65	1	S → L in MPH. Ref.4		VAR_016068
	Natural variant	80	1	R → Q in MPH; Gaza. Ref.1		VAR_006953
	Natural variant	80	1	R → W in MPH. Ref.5		VAR_006954
	Natural variant	130	1	N → S in MPH; Cambridge-1. Complete loss of activity. Ref.6		VAR_016069
	Natural variant	176	1	Q → P in MPH. Ref.4		VAR_016070
	Natural variant	203	1	A → V in MPH. Ref.1		VAR_006955
	Natural variant	205	1	V → E in MPH. Ref.4		VAR_016071
	Natural variant	208	1	F → I in MPH. Ref.4		VAR_016072
	Natural variant	215	1	E → D in MPH. Ref.4		VAR_016203
	Natural variant	232	1	S → L in MPH. Ref.1 Corresponds to variant rs28939085 [ dbSNP | Ensembl ].		VAR_006956
	Natural variant	235	1	M → V in MPH. Ref.1		VAR_006957
	Natural variant	268	1	C → Y in MPH; complete loss of activity. Ref.7		VAR_016073
	Natural variant	282	1	P → L in MPH. Ref.4		VAR_016074
	Natural variant	289	1	G → C. Corresponds to variant rs2066479 [ dbSNP | Ensembl ].		VAR_061844
	Natural variant	289	1	G → R. Corresponds to variant rs2066479 [ dbSNP | Ensembl ].		VAR_061845
	Natural variant	289	1	G → S. Ref.2 Ref.6 Corresponds to variant rs2066479 [ dbSNP | Ensembl ].		VAR_014871

Sequences

	Sequence		Length	Mass (Da)
	P37058 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: 0643FF35ED979185	FASTA	310	34,516
	10 20 30 40 50 60 MGDVLEQFFI LTGLLVCLAC LAKCVRFSRC VLLNYWKVLP KSFLRSMGQW AVITGAGDGI 70 80 90 100 110 120 GKAYSFELAK RGLNVVLISR TLEKLEAIAT EIERTTGRSV KIIQADFTKD DIYEHIKEKL 130 140 150 160 170 180 AGLEIGILVN NVGMLPNLLP SHFLNAPDEI QSLIHCNITS VVKMTQLILK HMESRQKGLI 190 200 210 220 230 240 LNISSGIALF PWPLYSMYSA SKAFVCAFSK ALQEEYKAKE VIIQVLTPYA VSTAMTKYLN 250 260 270 280 290 300 TNVITKTADE FVKESLNYVT IGGETCGCLA HEILAGFLSL IPAWAFYSGA FQRLLLTHYV 310 AYLKLNTKVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3." Geissler W.M., Davis D.L., Wu L., Bradshaw K.D., Patel S., Mendonca B.B., Elliston K.O., Wilson J.D., Russell D.W., Andersson S. Nat. Genet. 7:34-39(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MPH GLN-80; VAL-203; LEU-232 AND VAL-235. Tissue: Testis.
[2]	NIEHS SNPs program Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-31 AND SER-289.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency." Andersson S., Geissler W.M., Wu L., Davis D.L., Grumbach M.M., New M.I., Schwarz H.P., Blethen S.L., Mendonca B.B., Bloise W., Witchel S.F., Cutler G.B. Jr., Griffin J.E., Wilson J.D., Russel D.W. J. Clin. Endocrinol. Metab. 81:130-136(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MPH LEU-65; PRO-176; GLU-205; ILE-208; ASP-215 AND LEU-282.
[5]	"A novel missense (R80W) mutation in 17-beta-hydroxysteroid dehydrogenase type 3 gene associated with male pseudohermaphroditism." Bilbao J.R., Loridan L., Audi L., Gonzalo E., Castano L. Eur. J. Endocrinol. 139:330-333(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MPH TRP-80.
[6]	"Deleterious missense mutations and silent polymorphism in the human 17beta-hydroxysteroid dehydrogenase 3 gene (HSD17B3)." Moghrabi N., Hughes I.A., Dunaif A., Andersson S. J. Clin. Endocrinol. Metab. 83:2855-2860(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MPH THR-56 AND SER-130, VARIANT SER-289.
[7]	"Substitution mutation C268Y causes 17 beta-hydroxysteroid dehydrogenase 3 deficiency." Lindqvist A., Hughes I.A., Andersson S. J. Clin. Endocrinol. Metab. 86:921-923(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MPH TYR-268.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	U05659 mRNA. Translation: AAC50066.1. AY341031 Genomic DNA. Translation: AAP88937.1. BC034281 mRNA. Translation: AAH34281.1.
IPI	IPI00019871.
PIR	S43928.
RefSeq	NP_000188.1. NM_000197.1.
UniGene	Hs.477.
3D structure databases
ProteinModelPortal	P37058.
ModBase	Search...
Protein-protein interaction databases
IntAct	P37058. 1 interaction.
STRING	9606.ENSP00000364412.
PTM databases
PhosphoSite	P37058.
Polymorphism databases
DMDM	1169300.
Proteomic databases
PaxDb	P37058.
PRIDE	P37058.
Protocols and materials databases
DNASU	3293.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375263; ENSP00000364412; ENSG00000130948.
GeneID	3293.
KEGG	hsa:3293.
UCSC	uc004awa.1. human.
Organism-specific databases
CTD	3293.
GeneCards	GC09M098998.
HGNC	HGNC:5212. HSD17B3.
HPA	HPA015307.
MIM	264300. phenotype. 605573. gene.
neXtProt	NX_P37058.
Orphanet	752. 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency. 1331. Familial prostate cancer.
PharmGKB	PA29480.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0300.
HOGENOM	HOG000039237.
HOVERGEN	HBG005478.
InParanoid	P37058.
KO	K10207.
OMA	FPWPLYS.
OrthoDB	EOG4HMJB4.
PhylomeDB	P37058.
Enzyme and pathway databases
BioCyc	MetaCyc:HS05461-MONOMER.
Reactome	REACT_111217. Metabolism. REACT_15493. Steroid hormones.
UniPathway	UPA00367.
Gene expression databases
ArrayExpress	P37058.
Bgee	P37058.
CleanEx	HS_HSD17B3.
Genevestigator	P37058.
GermOnline	ENSG00000130948. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR002198. DH_sc/Rdtase_SDR. IPR002347. Glc/ribitol_DH. IPR016040. NAD(P)-bd_dom. IPR020904. Sc_DH/Rdtase_CS. [Graphical view]
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PIRSF	PIRSF000126. 11-beta-HSD1. 1 hit.
PRINTS	PR00081. GDHRDH. PR00080. SDRFAMILY.
PROSITE	PS00061. ADH_SHORT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P37058.
ChEMBL	CHEMBL4234.
DrugBank	DB00157. NADH.
GenomeRNAi	3293.
NextBio	13063.
SOURCE	Search...

Entry information

Entry name

DHB3_HUMAN

Accession

Primary (citable) accession number: P37058

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.